Hilton Lab

Matthew J. Hilton

Ph.D. 2004 University of Houston

Assistant Professor of Orthopaedics,
Director of Histology, Immunohisotchemistry,
and In Situ Hybridization Core,
Center for Musculoskeletal Research

Primary Appointment: Department of Orthopaedics

Center Affiliation: Center for Musculoskeletal Research

Research Overview

Most of the bones in the vertebrate skeleton arise from a cartilage template during embryogenesis. This process, known as endochondral ossification, begins with the differentiation of condensed mesenchymal stem cells (MSCs) into chondroprogenitors (immature cartilage cells) and osteoprogenitors (immature bone cells). Both the chondroprogenitor and osteoprogenitor cells undergo a coupled proliferation and differentiation program ultimately leading to the formation of mature cartilage and bone. Various genetic studies have demonstrated that Ihh, Pthrp, BMPs, FGFs, and canonical Wnt signaling pathways are required at multiple stages of normal cartilage and bone development. Deregulation of these signaling circuits during development are a primary cause for a variety of skeletal dysplasias, as well as, age related cartilage and bone pathologies.

A long-term interest of the Hilton lab is to uncover the molecular circuitry regulating lineage commitment, proliferation, and differentiation of MSCs and maturing chondrocytes. My laboratory uses genetic mouse models and primary cell culture techniques coupled with biochemistry to answer questions regarding MSC self-renewal/differentiation, chondrogenesis, and chondrocyte maturation. Recently my lab has generated novel data from a variety of Notch gain and loss-of-function mutant mice demonstrating that Notch signaling pathway suppresses MSC differentiation and plays critical roles in regulating chondrogenesis and chondrocyte maturation. We are currently investigating the exact Notch signaling mechanisms regulating both early and late stages of these processes, as well as, determining how Notch components interact with other known signaling pathways during cartilage development and maintenance. These studies are also being extended to aid in our mechanistic understanding of both fracture repair and osteoarthritis.

Finally, the Hilton lab is continuing to investigate the molecular mechanisms responsible for a developmental bone and cartilage disorder known as Multiple Hereditary Exostoses (MHE). MHE is an autosomal dominant disease caused by mutations in either the Ext1 or Ext2 genes, subunits of the heparan sulphate co-polymerase complex. Affected individuals are diagnosed with cartilaginous bony outgrowths (exostoses) adjacent to the growth plates of endochondral bones, bowing of some bones, and short stature. Although previous studies have shown that defects in Ext1 and Ext2 lead to reduced synthesis and shortened heparan sulphate chains on cell surface proteoglycans, the exact molecular mechanisms underlying this skeletal disease are still unknown. My lab is currently examining various Ext1 conditional mutant mouse models to determine the precise cell lineage and cause of exostosis formation. Additional genetic studies are also aimed at determining the effect that loss of Ext1 function has on specific signaling pathways important during chondrocyte and osteoblast development.


MSC Self-renewal and Differentiation
Growth plate
Growth Plate Cartilage
Development and Maturation
Fracture repair
Mechanisms of Fracture Repair
Articular cartilage
Articular Cartilage Development,
Maintenance, and Osteoarthritis

Recent Publications

Dong Y; Jesse AM; Kohn A; Gunnell LM; Honjo T; Zuscik MJ; O'Keefe RJ; Hilton MJ. "RBPj{kappa}-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development." Development (Cambridge, England). 2010; Epub 2010 Mar 24.

Gunnell LM; Jonason JH; Loiselle AE; Kohn A; Schwarz EM; Hilton MJ; O'Keefe RJ. "TAK1 regulates cartilage and joint Development via the MAPK and BMP signaling pathways." Journal of Bone and Mineral Research . 2010; Epub 2010 Mar 08.

Hilton MJ, Tu X, Bai S, Zhao H, Kobayashi T, Kronenberg HM, Teitelbaum SL, Ross FP, Kopan R, and Long F. (2008). Notch Signaling Maintains Bone Marrow Mesenchymal Progenitors by Suppressing Osteoblast Differentiation. Nature Medicine, 14 (3): 306-14.

Zuscik M, Hilton MJ, Zhang X, Chen D, and O’Keefe RJ. (2008). Regulation of Chondrogenesis and Chondrocyte Differentiation by Stress. Journal of Clinical Investigation, 118(2): 429-38.

Hilton MJ, Tu X, and Long F. (2007). Gene Deletion Using a Tamoxifen-inducible Col2-CreTM Transgenic Mouse Reveals Expression of Cola1(II)A Splice Form by Trabecular Osteoblastic Cells, and Direct Regulation of PTHrP Expression and Chondrocyte Morphology by Ihh. Developmental Biology, 308 (1): 93-105.

Hilton MJ, Tu X, Cook J, Hu H, and Long F. (2005). Ihh Controls Cartilage Development by Antagonizing Gli3 but Requires Additional Effectors to Regulate Osteoblast and Vascular Development. Development, 132(19):4339-51.

Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, and Long F. (2005). Sequential Roles of Hedgehog and Wnt Signaling in Osteoblast Development. Development, 132(1): 49-60.

Hilton MJ, Gutierrez L, Martinez D, and Wells DE. (2005). EXT1 Regulates Chondroctye Proliferation and Differentiation During Endochondral Bone Development. Bone, 36(3): 379-86.

More papers: PubMed

Graduate Program Affiliations


Matthew J. Hilton, Ph.D.
University of Rochester
601 Elmwood Ave., Box 665
Rochester, NY 14642
Office: SMD 1-8535
(585) 275-1335

Lab Members

Yufeng Dong

Yufeng Dong,
M.D., Ph.D.
Research Assistant Professor

Alana Jesse

Alana Jesse Laboratory Technician IV

Mohammed (Mahi) Rahman

Anat Kohn
M.D., Ph.D. student

Anthony Mirando Anthony J. Mirando, M.S.
Technical Associate I
Tim R
Timothy Rutkowski Ph.D. student
Z Liu

Zhaoyang Liu

Ph.D. student

C Wang

Cuicui Wang

Ph.D. student

open postdoctoral position